title: Immunoactivating peptide p4 augments alveolar macrophage phagocytosis in two diverse human populations.
abstract: New treatment strategies are urgently needed to overcome early mortality in acute bacterial infections. Previous studies have shown that administration of a novel immunoactivating peptide (P4) alongside passive immunotherapy prevents the onset of septicemia and rescues mice from lethal invasive disease models of pneumococcal pneumonia and sepsis. In this study, using two diverse populations of adult volunteers, we determined whether P4 treatment of human alveolar macrophages would upregulate phagocytic killing of Streptococcus pneumoniae ex vivo. We also measured macrophage intracellular oxidation, cytokine secretion, and surface marker expression following stimulation. Peptide treatment showed enhanced bacterial killing in the absence of nonspecific inflammation, consistent with therapeutic potential. This is the first demonstration of P4 efficacy on ex vivo-derived human lung cells.
authors.affiliation: Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bangert
authors.forename: Adam K
authors.initials: AK
authors.lastname: Wright
authors.forename: Jamie
authors.initials: J
authors.lastname: Rylance
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Kelly
authors.forename: Angela D
authors.initials: AD
authors.lastname: Wright
authors.forename: George M
authors.initials: GM
authors.lastname: Carlone
authors.forename: Jacquelyn S
authors.initials: JS
authors.lastname: Sampson
authors.forename: Gowrisankar
authors.initials: G
authors.lastname: Rajam
authors.forename: Edwin W
authors.initials: EW
authors.lastname: Ades
authors.forename: Aras
authors.initials: A
authors.lastname: Kadioglu
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D064368:Healthy Volunteers; D006801:Humans; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008295:Malawi; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000254:growth & development; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D016207:Cytokines; D009842:Oligopeptides; C560821:peptide P4